Project description:ObjectiveTo determine whether hypothalamus-pituitary-adrenal axis (HPAA) dysfunction is prospectively associated with global cognitive impairment in later life.MethodsThis cross-cohort study integrates 2 large longitudinal datasets, Whitehall II and the National Survey for Health and Development (NSHD), on data collected in the Whitehall II study between 2002-2004, 2007-2009, and 2012-2013; and for NSHD between 2006-2010 and in 2015. Serial salivary cortisol samples were collected multiple times within a 24-hour period at mean ages 61.2 and 65.9 years in Whitehall II and at age 60-64 years from NSHD participants. Cortisol profile is defined using cortisol awakening response and am:pm ratio. Cognitive function was measured using the Mini-Mental State Examination in Whitehall II and Addenbrooke's Cognitive Examination, third version, in NSHD, harmonized into a 30-point score. Models were adjusted for age, sex, diagnoses of hypertension and diabetes, body mass index (BMI), educational attainment, and interval between HPAA and cognitive assessments.ResultsIn fully adjusted models, increased am:pm cortisol ratio was prospectively associated with better later-life cognitive function years later (0.02 fewer errors per SD increase in am:pm cortisol ratio, p < 0.01) and verbal fluency (0.03 SD increase in verbal fluency per SD increase in am:pm ratio, p < 0.01). Increasing age, lower educational attainment, diagnosis of hypertension, diagnosis of diabetes, and increased BMI were associated with worse cognitive function and poorer verbal fluency. There were no associations between depression and later-life cognition or reverse associations between cognition and later-life cortisol profiles.ConclusionsLoss of diurnal HPAA variation is evident in individuals subsequently experiencing more cognitive impairment. It may serve as an early preclinical marker of cognitive decline.
Project description:ObjectiveTo determine whether breast feeding in infancy compared with bottle feeding formula milk is associated with lower mean blood pressure at different ages.DesignSystematic review.Data sourcesEmbase, Medline, and Web of Science databases.Study selectionStudies showing the effects of feeding in infancy on blood pressure at different ages.Data extractionPooled mean differences in blood pressure between breast fed infants and those bottle fed formula milk, based on random effects models.Data synthesisThe pooled mean difference in systolic blood pressure was -1.10 mm Hg (95% confidence interval -1.79 to -0.42 mm Hg) but with significant heterogeneity between estimates (P < 0.001). The difference was largest in studies of < 300 participants (-2.05 mm Hg, -3.30 to -0.80 mm Hg), intermediate in studies of 300-1000 participants (1.13 mm Hg, -2.53 to 0.27 mm Hg), and smallest in studies of > 1000 participants (-0.16 mm Hg, -0.60 to 0.28 mm Hg). An Egger test but not Begg test was statistically significant for publication bias. The difference was unaltered by adjustment for current size and was independent of age at measurement of blood pressure and year of birth. Diastolic blood pressure was not significantly related to type of feeding in infancy.ConclusionsSelective publication of small studies with positive findings may have exaggerated claims that breast feeding in infancy reduces systolic blood pressure in later life. The results of larger studies suggest that feeding in infancy has at most a modest effect on blood pressure, which is of limited clinical or public health importance.
Project description:In West Africa, the carriage of Group B Streptococcus (GBS), among infants is poorly characterised. We investigated co-carriage of GBS with other respiratory pathogens in the infants' nasopharynx in The Gambia.We assessed the carriage, serotypes and antibiotic susceptibility of Beta-haemolytic Streptococci (BHS) groups A-G; along with the carriage of Streptococcus pneumoniae; Haemophilus influenzae; Staphylococcus aureus and Moraxella catarrhalis in 1200 two-month old infants.The BHS prevalence was 20.0 % and GBS dominated (13.8 %), particularly serotypes V and II; serotype V being negatively associated with H. Influenzae carriage (OR 0.41 [95 % CI: 0.18-0.93], p = 0.033). Although co-colonization of GBS and other BHS was not seen, colonization with GBS was positively associated with S. aureus (OR 1.89 [95 % CI: 1.33-2.69], P < 0.001) and negatively associated with S. pneumoniae (OR 0.47 [95 % CI: 0.33-0.67], p < 0.001) and M. catarrhalis (OR 0.61 [95 % CI: 0.40-0.92], p = 0.017). ? 89 % of GBS isolates were susceptible to most antibiotics tested, except for tetracycline resistance, which was 89 %.This study provides baseline data on the carriage of GBS in two month old infants from West Africa. The dominant serotypes of GBS in this setting are serotypes V and II. This may be important for future GBS vaccine development for the West African sub-region.
Project description:BackgroundAge-related changes in cognitive and balance capabilities are well-established, as is their correlation with one another. Given limited evidence regarding the directionality of associations, we aimed to explore the direction and potential explanations of associations between word memory and one-legged balance performance in mid-later life.MethodsA total of 3062 participants in the Medical Research Council National Survey of Health and Development, a British birth cohort study, were included. One-legged balance times (eyes closed) were measured at ages 53, 60-64 and 69 years. Word memory was assessed at ages 43, 53, 60-64 and 69 with three 15-item word-recall trials. Autoregressive cross-lagged and dual change score models assessed bidirectional associations between word memory and balance. Random-effects models quantified the extent to which these associations were explained by adjustment for anthropometric, socioeconomic, behavioural and health status indicators.ResultsAutoregressive cross-lagged and dual change score models suggested a unidirectional association between word memory and subsequent balance performance. In a sex-adjusted random-effects model, 1 standard deviation increase in word memory was associated with 9% (7,12%) higher balance performance at age 53. This association decreased with age (-0.4% /year (-0.6,-0.1%). Education partially attenuated the association, although it remained in the fully-adjusted model (3% (0.1,6%)).ConclusionsThere was consistent evidence that word memory is associated with subsequent balance performance but no evidence of the reverse association. Cognitive processing plays an important role in the balance process, with educational attainment providing some contribution. These findings have important implications for understanding cognitive-motor associations and for interventions aimed at improving cognitive and physical capability in the ageing population.
Project description:Evidence has linked sporting leisure time physical activity (sporting-LTPA) to healthy cognition throughout adulthood. This may be due to the physiological effects of physical activity (PA), or to other, psychosocial facets of sport. We examined associations between sporting-LTPA and cognition while adjusting for device-measured PA volume devoid of context, both in midlife (N = 4041) participants from the 1970 British Cohort Study and later-life (N = 957) participants from the British Regional Heart Study. Independent of device-measured PA, we identified positive associations between sporting-LTPA and cognition. Sports with team/partner elements were strongly positively associated with cognition, suggesting LTPA context may be critical to this relationship.
Project description:BackgroundIdentifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms and highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites and whole-brain volume, hippocampal volume, and amyloid-β status among participants of Insight 46-the neuroscience sub-study of the National Survey of Health and Development (NSHD). We additionally explored whether key metabolites were associated with polygenic risk for Alzheimer's disease (AD).MethodsFollowing quality control, levels of 1019 metabolites-detected with liquid chromatography-mass spectrometry-were available for 1740 participants at age 60-64. Metabolite data were subsequently clustered into modules of co-expressed metabolites using weighted coexpression network analysis. Accompanying MRI and amyloid-PET imaging data were present for 437 participants (age 69-71). Regression analyses tested relationships between metabolite measures-modules and hub metabolites-and imaging outcomes. Hub metabolites were defined as metabolites that were highly connected within significant (pFDR < 0.05) modules or were identified as a hub in a previous analysis on cognitive function in the same cohort. Regression models included adjustments for age, sex, APOE genotype, lipid medication use, childhood cognitive ability, and social factors. Finally, associations were tested between AD polygenic risk scores (PRS), including and excluding the APOE region, and metabolites and modules that significantly associated (pFDR < 0.05) with an imaging outcome (N = 1638).ResultsIn the fully adjusted model, three lipid modules were associated with a brain volume measure (pFDR < 0.05): one enriched in sphingolipids (hippocampal volume: ß = 0.14, 95% CI = [0.055,0.23]), one in several fatty acid pathways (whole-brain volume: ß = - 0.072, 95%CI = [- 0.12, - 0.026]), and another in diacylglycerols and phosphatidylethanolamines (whole-brain volume: ß = - 0.066, 95% CI = [- 0.11, - 0.020]). Twenty-two hub metabolites were associated (pFDR < 0.05) with an imaging outcome (whole-brain volume: 22; hippocampal volume: 4). Some nominal associations were reported for amyloid-β, and with an AD PRS in our genetic analysis, but none survived multiple testing correction.ConclusionsOur findings highlight key metabolites, with functions in membrane integrity and cell signalling, that associated with structural brain measures in later life. Future research should focus on replicating this work and interrogating causality.
Project description:ObjectivesThis study examined whether childhood chronic physical illness burden was associated with major depression in later life (>50 years) and whether this relationship was mediated by childhood mental health status.MethodData came from the 2016 United States Health and Retirement Study (n = 18,483). Logistic regression tested associations of childhood chronic physical illness burden with childhood mental health status and major depression in later life. Path analysis quantified mediation of the association between chronic physical illness burden and major depression by childhood mental health status.ResultsOne standard deviation increase in childhood chronic physical illness burden was associated with 1.34 (95% CI = 1.25, 1.43) times higher odds of major depression in later life. Childhood mental health status explained 53.4% (95% CI: 37.3%, 69.6%) of this association. In follow-up analyses of categorical diagnoses, having difficulty seeing, ear problems or infections, a respiratory disorder, asthma, an allergic condition, epilepsy or seizures, migraines or severe headaches, heart trouble, stomach problems, or a disability lasting ≥6 months was associated with major depression in later life with mediation by childhood mental health status.ConclusionFindings of this study indicate that children with a higher chronic physical illness burden are more likely to have major depression in later life and poor mental health during childhood mediates this relationship. Further research is needed to determine whether increased screening and treatment of psychiatric symptoms in pediatrics can decrease the burden of major depression across the life course.
Project description:ImportanceEvidence linking parental socioeconomic position and offspring's schizophrenia risk has been inconsistent, and how risk is associated with parental socioeconomic mobility has not been investigated.ObjectiveTo elucidate the association between parental income level and income mobility during childhood and subsequent schizophrenia risk.Design, setting, and participantsNational cohort study of all persons born in Denmark from January 1, 1980, to December 31, 2000, who were followed up from their 15th birthday until schizophrenia diagnosis, emigration, death, or December 31, 2016, whichever came first. Data analyses were from March 2018 to June 2019.ExposureParental income, measured at birth year and at child ages 5, 10, and 15 years.Main outcomes and measuresHazard ratios (HRs) for schizophrenia were estimated using Cox proportional hazard regression. Cumulative incidence values (absolute risks) were also calculated.ResultsThe cohort included 1 051 033 participants, of whom 51.3% were male. Of the cohort members, 7544 (4124 [54.7%] male) were diagnosed with schizophrenia during 11.6 million person-years of follow-up. There was an inverse association between parental income level and subsequent schizophrenia risk, with children from lower income families having especially elevated risk. Estimates were attenuated, but risk gradients remained after adjustment for urbanization, parental mental disorders, parental educational levels, and number of changes in child-parent separation status. A dose-response association was observed with increasing amount of time spent in low-income conditions being linked with higher schizophrenia risk. Regardless of parental income level at birth, upward income mobility was associated with lower schizophrenia risk compared with downward mobility. For example, children who were born and remained in the lowest income quintile at age 15 years had a 4.12 (95% CI, 3.71-4.58) elevated risk compared with the reference group, those who were born in and remained in the most affluent quintile, but even a rise from the lowest income quintile at birth to second lowest at age 15 years appeared to lessen the risk elevation (HR, 2.80; 95% CI, 2.46-3.17). On the contrary, for those born in the most affluent quintile, downward income mobility between birth and age 15 years was associated with increased risks of developing schizophrenia.Conclusions and relevanceThis study's findings suggest that parental income level and income mobility during childhood may be linked with schizophrenia risk. Although both causation and selection mechanisms could be involved, enabling upward income mobility could influence schizophrenia incidence at the population level.
Project description:BackgroundPoor parental bonding in childhood has been associated with loneliness in younger populations. Whether these associations persists into middle and older adulthood is unclear. Additionally, given the overlapping relationship between loneliness and social isolation we sought to explore the role of social isolation in any associations present i.e. are those reporting worse parental bonding lonely due to less connections or are they more likely to be lonely regardless of isolation.MethodsAnalysis of a nationally representative longitudinal sample of adults aged 50 and over from the English Longitudinal Study of Ageing was undertaken. The current analysis was based on data for core participants across waves 3[2006/7] to 8[2016/17] with missing data across waves leading to analytical samples ranging from 4384 to 5173. Multivariate adjusted multinomial regression models were used to assess associations between parental bonding [PBI], isolation [score derived from data on living alone, frequency of contact with friends, family and children, and whether or not participate in social organisations] and loneliness [R-UCLA].ResultsParental bonding scores were associated with later life loneliness according to overall PBI score [RRR .93 95%CI .92-.95], care [RRR .90 95%CI .88-.92] and overprotection [RRR 1.11 95%CI 1.08-1.14] subscale scores as well as when separated into maternal and paternal scores, with effects larger in relation to chronic loneliness. Parental bonding scores were also associated with isolation in later life, with the exception of maternal overprotection which was non-significant. The addition of isolation to the loneliness models however had no impact on associations indicating that isolation is not a mediator of the association between parental bonding and later life loneliness.ConclusionsAssociations between parental bonding and loneliness do persist into middle and older adulthood and were in line with hypothesis stronger for more chronic loneliness. Isolation did not explain these associations and those reporting more negative parental bonds were more likely to be lonely regardless of isolation.